Did the office telephone
lines start buzzing when the media broadcasted reports of adverse events linked
to use of the transdermal contraceptive Ortho Evra (Ortho-McNeil Pharmaceutical,
Raritan, NJ)? There’s no doubt that clinicians have, since those reports, fielded
many questions about the safety of the patch, which has been used by about 4
million women since its November 2001 approval by the Food and Drug Administration
(FDA).

Media reports were prompted
by the April 2004 death of an 18-year-old New York City woman who had been using
the transdermal contraceptive. An autopsy indicated the cause of death was due
to a pulmonary embolism, and the medical examiner ruled it a side effect of
the birth control device. The New YorkPost published a report
stating that it had obtained FDA records "show[ing] that 17 patch users, ages
17 to 30, suffered fatal heart attacks, blood clots, and possible strokes since
August 2002."1

The FDA and Ortho-McNeil
are examining the adverse event reports; however, both believe that the published
numbers may contain duplications, states Kathleen Quinn, agency spokeswoman.

"FDA does not see any safety
differences between the patch and pill when it comes to mortality/morbidity,"
states Quinn. "We will, like with all drugs, continue to monitor the issue and
take what action is necessary, if any."

Ortho-McNeil is making
the warning information about the risks of Evra use more prominent on its web
site, www.orthoevra.com,
says Doug Arbesfeld, company spokesman. "Our representatives are talking
to providers, reviewing the data with them, and assuring them that we take this
very seriously and that we are investigating it," he adds.

Check talking points

The Washington, DC-based
Association of Reproductive Health Professionals (ARHP) has issued a set of
"talking points" to help clinicians discuss the media reports with their patients.
The professional association maintains that "the [New York Post] article
is biased and unfortunate, misrepresenting the available data and presenting
a skewed picture of adverse events attributable to the contraceptive patch in
particular, and medications in general."2

Possible adverse drug reports
are submitted voluntarily to FDA by clinicians in the United States and are
intended to provide a means to identify rare medical problems that had not been
anticipated in the clinical studies undertaken for FDA drug approval, the ARHP
publication points out.

"Serious medical events
are reported whether or not there is a clear cause-and-effect connection to
the drug," states the publication. "For any medication that is widely used,
therefore, at least some deaths are bound to occur and be reported."

When talking with patients
about use of combined hormonal contraception, which includes oral contraceptives
as well as the contraceptive vaginal ring (NuvaRing, Organon, West Orange, NJ),
the ARHP advises the following discussion points:

Deaths among young women
because of medical problems such as heart attack are very rare, and they also
are very rare among young women using contraceptive hormones.

The rate for cardiovascular
problems estimated for women using the patch is in the range that has been
reported for other hormonal contraceptives such as oral contraceptives.

Health risks for patch
users essentially are the same as risks for women using other hormonal contraceptives.

In context, risks for
death associated with other common activities such as driving an automobile
(1 in 5,900) or continuing a pregnancy to term (1 in 10,000) are significantly
higher than risks associated with use of hormonal contraceptives.

The risk of death associated
with pregnancy — a common outcome among women who don’t use contraception
— is far higher than the risk of death associated with using contraceptive
pills or the patch. Pregnancy-related deaths, including those at delivery,
stillbirth, and ectopic pregnancy, claim the lives of two to three U.S. women
every day, with 13 deaths reported for every 100,000 live births in 1999.2

How to explain risks

Robert Hatcher,
MD, MPH, professor of gynecology and obstetrics at Emory University School of
Medicine in Atlanta, uses the risk tables published in the latest edition of
Contraceptive Technology to help explain the risks of patch use3:

If 2 million women become
pregnant over a one-year period and carry their pregnancies to term, then
one woman out of each 10,000 will die. Of the 2 million women who have become
pregnant, 200 will die. If another 2 million women became pregnant the next
year, another 200 would die, for a total of 400 deaths in two years.

If 200,000 nonsmoking
women younger than 35 years of age use pills to prevent pregnancy for one
year, then one woman will die. Therefore, if 2 million women use birth control
pills for one year, then 10 women will die. If 2 million nonsmoking women
use birth control pills for two years, then 20 will die.

If 5,300 women who smoke
heavily and are younger than 35 years of age use pills for a year, then one
will die. If 2 million who smoke heavily and are younger than the age of 35
use birth control pills for two years, then about 750 will die.

So the number of deaths
for 2 million nonsmoking women who use pills for a year would be about 20;
whereas, if they were heavy smokers, the number of deaths would be 750.

"The New York Post
article found 17 deaths among 2 million women using the patch over a two-year
period," Hatcher observes. "This is clearly far fewer deaths than would have
occurred if 2 million women had become pregnant each of two years [400 deaths]."

Seventeen deaths among
2 million patch users over a two-year period is in the range of deaths to be
expected if those same 2 million women (most of whom were nonsmokers, but some
of whom were heavy smokers) were to have used pills for two years, comments
Hatcher.

"The New York Post
article underscores the point that deaths and very serious complications may
occur from a contraceptive like the patch, but that the risk of death from using
the patch is far, far less than the risk of death from pregnancy," he notes.

Talk about ACHES’

The patch, like other forms
of combined hormonal contraceptives, carries risks; these risks are spelled
out in the product labeling and package insert. The most commonly reported adverse
reactions in Evra’s clinical trials included breast symptoms, headache, application-site
reactions, nausea and vomiting, dysmenorrhea, and abdominal pain.4,5
In clinical trials, the contraceptive patch was shown to have comparable safety
and efficacy with that of oral contraceptives.6

Smoking, hypertension,
obesity, and diabetes are risk factors that must be taken into account when
prescribing any form of combined oral contraception.7 When providing
counseling on combined hormonal contraceptive use, whether patch, pill, or ring,
providers should use the "ACHES" mnemonic to teach women potential danger signals:

Abdominal pain;

Chest pain;

Headaches that
are severe;

Eye problems;

Severe leg pain.3

Giving women the information
they need to monitor themselves can minimize the risks of any method. The ACHES
mnemonic is easy to recall and to teach, says Linda Dominguez, RNC, NP,
assistant medical director of the Albuquerque-based Planned Parenthood of New
Mexico. The information fits nicely on a small wallet card that can be personalized
with the clinic/office contact information as well as individual health information
such as current weight, blood pressure reading, or lab values, she advises.

"This minichart information
written on the back of the card will be of interest to the patient and will
bring her attention back to the ACHES teaching method as well," she states.